The invention relates to platinum complex compounds of substituted 5,8-dihydroxyl-1,4-naphthoquinones and also to a process for their manufacture and their use as materials with an antitumor effect.
It is known that a number of platinum compounds, particularly cis-dichloro-diamino-platinum (II), used in clinics under the name cis-DDP, along with its generally toxic effect and also bactericidal, virusidal and immuno-suppressive effects, also has an antitumor effect (Rosenberg, Naturwissenschaften 1973, 399-406). It is also known that complexes of this quadratic planar platinum compound with anthraquinone derivatives such as quinizarin and doxorubizin discharge the cis-DDP in the animal body slowly, and its toxicity is greatly decreased. While more than 7 mg of the free cis-DDP/kg of mouse has a toxic effect, doses of 20 mg of cis-DDP/kg mouse can be applied by using the new complex compounds, and this promotes both an increase of the average survival time and also an increased number of cases of healing. In the course of the testing of the pharmacological effect of the cited platinum-anthraquinone complexes, for the purpose of clarification of the chemical bonding ratios, some relatively simple alpha-hydroxylquinones were also complexed with platinum, but were tested neither in vitro nor in vivo on tumors or for other pharmacological effect (Yolles et al., ACS-Symposium 1982, 233-241). With these naphthoquinone complexes manufactured only for the structural definition, the complexes involved were:
(I) 5-hydroxyl-1,4-naphthoquinone/cis-DDP complex PA0 (II) 5,8-dihydroxyl-1,4-naphthoquinone/cis-DDP complex.